Conventionally, cancer (malignant tumors) has been treated through surgical therapy, chemotherapy, immunotherapy, thermal therapy, and radiotherapy. In progressive stages III and IV, cancers such as stomach cancer, rectal cancer, pancreatic cancer, head and neck cancer, esophageal cancer, lung cancer, and breast cancer are usually treated through radiation therapy. Radiation therapy (currently total clinical radiation dose of 40 to 60 Gy) is difficult to employ singly for a long period of time, due to blood toxicity and adverse effects on the digestive system (e.g., thirst). Therefore, radiation therapy provides an insufficient clinical effect (anti-tumor effect). In recent years, in order to attain high anti-tumor effects, a combination of a chemotherapeutic agent and radiation (i.e., chemoradiotherapy) has become a standard treatment, and the combined treatment is thought to be successful in cancer treatment, as compared with the case of sole radiation therapy or sole chemotherapy (Non-Patent Document 1). For example, the following cases are disclosed: a combination of carboplatin/fluorouracil and radiation (Non-Patent Document 2) and a combination of cisplatin and radiation in the treatment of head and neck cancer (Non-Patent Document 3); a combination of fluorouracil/cisplatin and radiation in the treatment of esophageal cancer (Non-Patent Document 4); a combination of fluorouracil and radiation in the treatment of pancreatic cancer (Non-Patent Document 5); and a combination of cisplatin/vinblastine and radiation in the treatment of non-small-cell lung cancer (Non-Patent Document 6). In those cases, survival time is significantly prolonged as compared with sole radiation therapy. In the treatment of rectal cancer, patients who have been received chemoradiotherapy after surgery exhibit lower percent recurrence and have longer survival time, as compared with similar patients who have not received chemoradiotherapy (Non-Patent Document 7). However, currently, combined therapy of a chemotherapeutic agent and radiotherapy may cause adverse effects attributed to the chemotherapeutic agent itself, and in some cases medical treatment must be interrupted. In addition, mitigation of such adverse effects has not been fully attained.
Various attempts have been made to provide radiation sensitizers, which reduce radiation dose to thereby mitigate adverse effects without impairing radiation therapeutic effect. For example, certain nitroimidazole derivatives are known to serve as radiation sensitizers, and compounds such as misonidazole and etanidazole have been provided. However, such compounds have drawbacks; for example, excessively strong neurotoxicity when employed at a dose for attaining sensitization activity, and therefore cannot be used in practice. Meanwhile, in the treatment of a radiation-resistant tumor, a drug that potentiates radiation sensitivity is preferably used in combination. However, most of the reported radiation therapy potentiators (radiation sensitizers and similar agents) have neurotoxicity, which impedes development of radiation sensitizers.
[Non-Patent Document 1]
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